rs147692085
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000430.4(PAFAH1B1):c.118-14T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,476,616 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0043 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00072 ( 3 hom. )
Consequence
PAFAH1B1
NM_000430.4 splice_polypyrimidine_tract, intron
NM_000430.4 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.164
Genes affected
PAFAH1B1 (HGNC:8574): (platelet activating factor acetylhydrolase 1b regulatory subunit 1) This locus was identified as encoding a gene that when mutated or lost caused the lissencephaly associated with Miller-Dieker lissencephaly syndrome. This gene encodes the non-catalytic alpha subunit of the intracellular Ib isoform of platelet-activating factor acteylhydrolase, a heterotrimeric enzyme that specifically catalyzes the removal of the acetyl group at the SN-2 position of platelet-activating factor (identified as 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine). Two other isoforms of intracellular platelet-activating factor acetylhydrolase exist: one composed of multiple subunits, the other, a single subunit. In addition, a single-subunit isoform of this enzyme is found in serum. [provided by RefSeq, Apr 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
?
Variant 17-2666002-T-C is Benign according to our data. Variant chr17-2666002-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 256109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-2666002-T-C is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00429 (654/152306) while in subpopulation AFR AF= 0.0136 (566/41562). AF 95% confidence interval is 0.0127. There are 1 homozygotes in gnomad4. There are 293 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 651 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PAFAH1B1 | NM_000430.4 | c.118-14T>C | splice_polypyrimidine_tract_variant, intron_variant | ENST00000397195.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PAFAH1B1 | ENST00000397195.10 | c.118-14T>C | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000430.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00428 AC: 651AN: 152188Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00133 AC: 237AN: 178042Hom.: 1 AF XY: 0.00104 AC XY: 100AN XY: 95894
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GnomAD4 exome AF: 0.000720 AC: 954AN: 1324310Hom.: 3 Cov.: 28 AF XY: 0.000680 AC XY: 445AN XY: 653948
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GnomAD4 genome ? AF: 0.00429 AC: 654AN: 152306Hom.: 1 Cov.: 32 AF XY: 0.00393 AC XY: 293AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 16, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at